Polymorphism E23K KCNJ11 Gen as a Risk Factor of Diabetes Mellitus in Serawai Tribe Of Bengkulu

ABSTRACT Background: Type 2 diabetes mellitus (T2DM) is a multifactorial disease involving genetic and environmental factors. The E23K KCNJ11 gene polymorphism causes KATP canal overactivity, decreases cell membrane depolarization potential, and decreases insulin secretion. E23K polymorphism of the KCNJ11 gene as a risk factor for T2DM. Research Objective: This study aimed to analyze the E23K polymorphism of the KCNJ11 gene as a risk factor for T2DM in the Bengkulu Serawai. Method: This study is a case-control study. The subjects of the study were 100 people with T2DM patients as a case group (50 people) and Non-DM subjects with families who did not have a history of T2DM as a control group (50 people). Fasting blood glucose (GDP) was analyzed by spectrophotometry and E23K KCNJ11 gene by polymerase chain reaction fragment length polymorphism (PCR-RFLP). Data were analyzed by statistics. Results: The frequency of AA genotypes in cases was higher than the controls (12% and 8%) (p = 0.001). The frequency of A allele in the case was higher than the control (32% and 18%) (p = 0.017). The risk of T2DM on AA / GA genotypes was 4.75 times higher in cases than controls (p = 0,000, OR 4.75 95% CI 2.01-11.24). The risk of T2DM in A allele was 2.14 times higher in cases than in controls (p = 0.017, OR 2.14, 95% CI 1.11-4.15). Conclusion: E23K polymorphism of the KCNJ11 gene as a risk factor for T2DM in Bengkulu Serawai Tribe. Keywords: E23K gene KCNJ11, DMT2, Non-DMT2.

Search for Pharmacoepigenetic Correlations in Type 2 Diabetes Under Sulfonylurea Treatment

Sulfonylureas are insulin secretagogues which act in pancreatic β cells by blocking the KATP channels encoded by KCNJ11 and ABCC8 genes. In the present study, a pharmacoepigenetic approach was applied for the first time, investigating the correlation of KCNJ11 and ABCC8 gene promoter methylation with sulfonylureas-induced mild hypoglycemic events as well as the KCNJ11 E23K genotype. Sodium bisulfite-treated genomic DNA of 171 sulfonylureas treated T2DM patients previously genotyped for KCNJ11 E23K, including 88 that had experienced drug-associated hypoglycemia and 83 that had never experienced hypoglycemia, were analyzed for DNA methylation of KCNJ11 and ABCC8 gene promoters via quantitative Methylation-Specific PCR. KCNJ11 methylation was detected in 19/88 (21.6%) of hypoglycemic and in 23/83 (27.7%) of non-hypoglycemic patients (p=0.353), while ABCC8 methylation in 6/83 (7.2%) of non-hypoglycemic and none (0/88) of the hypoglycemic patients (p=0.012). Methylation in at least one promoter (KCNJ11 or ABCC8) was significantly associated with non-hypoglycemic patients who are carriers of KCNJ11 EK allele (p=0.030). Our data suggest that ABCC8 but not KCNJ11 methylation is associated to hypoglycemic events in sulfonylureas-treated T2DM patients. Furthermore, it is demonstrated that the KCNJ11 E23K polymorphism in association to either of the two genes’ DNA methylation may have protective role against sulfonylurea-induced hypoglycemia.

Association Between KCNJ11 Gene E23K Polymorphism and Body Composition Together with Its Response to Endurance Training

To explore the association between KCNJ11 gene E23K polymorphism of Chinese and body composition together with its response to endurance training. 102 biologically unrelated Han nationality male new recruits from northern China volunteered to execute a 5000-m running program, and the intensity is 95–105% individual lactate threshold. The protocol was lasted for 18 weeks, three times per week. The body composition index, including body weight (WT), lean body weight (LBW), body mass index (BMI) and body fat percentage (Fat%), was measured before and after training. PCR-RFLP was used to detect the KCNJ11 gene E23K polymorphism. Hardy-Weinberg equilibrium was observed for the frequency of genotypes in these subjects. Before training, WT, BMI and Fat% in KK group were significantly higher than those in EE and KK group (P<0.05 or P<0.01). There was no significant difference in LBW among groups (P>0.05). After training, the changes of all body composition index in KK group were bigger significantly greater than those in EE and EK groups (P<0.01). KCNJ11 gene E23K polymorphism might contribute to individual body composition together with its response to endurance training. The body fat content at baseline in KK was more than those in EE and EK groups, and it may hinder that individual to eliminate their body fat during endurance training.

Genetic Variations in the Kir6.2 Subunit(KCNJ11)of Pancreatic ATP-Sensitive Potassium Channel Gene Are Associated with Insulin Response to Glucose Loading and Early Onset of Type 2 Diabetes in Childhood and Adolescence in Taiwan

To investigate the role of E23K polymorphism of theKCNJ11gene on early onset of type 2 diabetes in school-aged children/adolescents in Taiwan, we recruited 38 subjects with type 2 diabetes (ages 18.6 ± 6.6 years; body mass index percentiles 83.3 ± 15.4) and 69 normal controls (ages 17.3 ± 3.8 years; body mass index percentiles 56.7 ± 29.0) from a national surveillance for childhood/adolescent diabetes in Taiwan. We searched for the E23K polymorphism of theKCNJ11gene. We found that type 2 diabetic subjects had higher carrier rate of E23K polymorphism ofKCNJ11gene than control subjects (P= 0.044). After adjusting for age, gender, body mass index percentiles, and fasting plasma insulin, the E23K polymorphism contributed to an increased risk for type 2 diabetes (P= 0.047). K23-allele-containing genotypes conferring increased plasma insulin level during OGTT in normal subjects. However, the diabetic subjects with the K23-allele-containing genotypes had lower fasting plasma insulin levels after adjustment of age and BMI percentiles. In conclusion, the E23K variant of theKCNJ11gene conferred higher susceptibility to type 2 diabetes in children/adolescents. Furthermore, in normal glucose-tolerant children/adolescents, K23 allele carriers had a higher insulin response to oral glucose loading.